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Research Article: Association of age at menopause with cardiovascular disease and mortality: insights from NHANES and a clinical cohort

Date Published: 2026-06-23

Abstract:
Age at menopause is closely associated with cardiovascular disease and mortality, whereas the underlying mechanisms remain unclear. This study employed mediation analysis to explore potential pathways underlying this association. Natural postmenopausal women were identified from the NHANES database to assess the association between age at menopause and cardiovascular disease and mortality. Mediation analysis was performed to identify potential mediators. A hospital-based cohort was used for a supportive analysis. Compared with women with menopause at 50–51 years, those with menopause before 40 years had a higher prevalence of cardiovascular disease and increased risks of all-cause and cardiovascular mortality. Dose–response analysis indicated that each one-year decrease in age at menopause was associated with 3%, 3%, and 4% increases in cardiovascular disease prevalence, all-cause mortality, and cardiovascular mortality, respectively. Mediation analysis showed that total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), hypertension, and glycated hemoglobin partially mediated the association between age at menopause and adverse outcomes. A hospital-based cohort study further supported these findings. Early menopause is significantly associated with higher cardiovascular disease prevalence, all-cause mortality, and cardiovascular mortality, and this association is partially mediated by metabolic dysregulation.

Introduction:
Age at menopause is closely associated with cardiovascular disease and mortality, whereas the underlying mechanisms remain unclear. This study employed mediation analysis to explore potential pathways underlying this association.

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